This article is more than 5 years old. Information may no longer be current.
Meta-analysis: PCSK9 inhibitors reduce mortality, MI
Click Here to Manage Email Alerts
According to a systematic review and meta-analysis of trials of PCSK9 inhibitors, the novel cholesterol-lowering agents are associated with reductions in mortality and MI.
Researchers analyzed 24 phase 2 and phase 3 trials of the PCSK9 inhibitors alirocumab (Sanofi-Regeneron) and evolocumab (Amgen), both fully human monoclonal antibodies, covering 10,159 participants.
Primary endpoints were all-cause mortality and CV mortality. Secondary endpoints included MI, unstable angina, increased serum creatinine kinase level and serious adverse events. The main efficacy endpoints were percent change from baseline in LDL and HDL levels. Most trials included patients who had been treated with statins but had not met target LDL goals, although some included patients intolerant to statins; control groups were assigned placebo or ezetimibe (Zetia, Merck).
According to the analysis by Eliano Pio Navarese, MD, PhD, and colleagues, patients assigned PCSK9 antibodies had marked reductions in LDL levels (mean difference, –47.49%; 95% CI, –69.64 to –25.35) and other atherogenic lipid fractions, compared with those not assigned PCSK9 antibodies. Assignment to PCSK9 antibody was associated with an increase of 6.3% (95% CI, 5.58-7.02) in HDL compared with controls.
Eliano Pio Navarese
Mortality reduction
Assignment to PCSK9 antibodies was associated with reduction in all-cause mortality (PCSK9 groups, 0.31%; control groups, 0.53%; OR = 0.45; 95% CI, 0.23-0.86), CV mortality (PCSK9 groups, 0.19%; control groups, 0.33%; OR = 0.5; 95% CI, 0.23-1.1) and MI (PCSK9 groups, 0.58%; control groups, 1%; OR = 0.49; 95% CI, 0.26-0.93).
The six trials that reported data on unstable angina found no difference between those assigned PCSK9 antibodies and controls (PCSK9 groups, 0.04%; control groups, 0.08%; OR = 0.61; 95% CI, 0.06-6.14).
Navarese and colleagues also found that increases in serum kinase level were reduced in patients assigned PCSK9 antibodies (OR = 0.72; 95% CI, 0.54-0.96), and that serious adverse events did not increase with administration of PCSK9 antibodies (PCSK9 groups, 9.26%; control groups, 7.73%; OR = 1.01; 95% CI, 0.87-1.18).
“Our large-scale report is the first to show a benefit in mortality with these novel agents,” Navarese, from the department of internal medicine, division of cardiology, pulmonology and vascular medicine, Heinrich Heine University, Düsseldorf, Germany, and colleagues wrote. “The finding of lower all-cause mortality, although preliminary, is encouraging and is further corroborated by a similar direction in the reduction of odds of [CV] mortality, as well as by recent findings of the open-label OSLER-1 and OSLER-2 extension trials that showed reductions in [CV] events with evolocumab compared with standard therapy.”
Cautious interpretation
In a related editorial, Miguel Cainzos-Achirica, MD, and colleagues noted that these “encouraging” results “warrant cautious interpretation.”
“Included trials were of small or moderate size and mostly had short follow-up periods. The total number of events was small (for example, the results for all-cause mortality were based on only 40 events), several studies did not report any events at all, and quantitative pooling of rare events remains a challenging task. Moreover, the trials that were summarized were not specifically designed or powered to detect differences in clinical outcomes or rare adverse events,” they wrote.
Cainzos-Achirica, from Johns Hopkins Medical Institutions, and colleagues concluded that “confirmation of these findings in long-term, ongoing, pivotal trials with prespecified primary CVD endpoints and a monitoring of a broad range of adverse events will help establish the role of these novel agents in CVD risk management.” – by Erik Swain
Disclosure: One researcher reports receiving consulting fees from Sanofi. One editorial writer reports being listed as a co-inventor on a pending patent filed by Johns Hopkins University for a novel method of LDL estimation.
Click Here to Manage Email Alerts